Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model.
Bacterial drug resistance is often associated with a fitness cost. Large outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been described that predominately affect persons with HIV infection. We obtained four closely-related Mycobacterium tuberculosis strains (genot...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3986381?pdf=render |
| _version_ | 1818889949225680896 |
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| author | Kristen L Jurcic Smith Divey Saini Svetoslav Bardarov Michelle Larsen Richard Frothingham Neel R Gandhi William R Jacobs A Willem Sturm Sunhee Lee |
| author_facet | Kristen L Jurcic Smith Divey Saini Svetoslav Bardarov Michelle Larsen Richard Frothingham Neel R Gandhi William R Jacobs A Willem Sturm Sunhee Lee |
| author_sort | Kristen L Jurcic Smith |
| collection | DOAJ |
| description | Bacterial drug resistance is often associated with a fitness cost. Large outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been described that predominately affect persons with HIV infection. We obtained four closely-related Mycobacterium tuberculosis strains (genotype F15/LAM4/KZN) from an outbreak in KwaZulu-Natal (KZN), South Africa, including drug-sensitive, MDR, and XDR clinical isolates. We compared the virulence of these strains in a murine model of aerosol M. tuberculosis infection for four phenotypes: (1) competitive in vivo growth in lung and spleen, (2) non-competitive in vivo growth in lung and spleen, (3) murine survival time, and (4) lung pathology. When mixtures of sensitive, MDR, and XDR KZN strains were aerosolized (competitive model), lung CFUs were similar at 60 days after infection, and spleen CFUs were ordered as follows: sensitive > MDR > XDR. When individual strains were aerosolized (non-competitive model), modest differences in lung and spleen CFUs were observed with the same ordering. C57BL/6, C3H/FeJ, and SCID mice all survived longer after infection with MDR as compared to sensitive strains. SCID mice infected with an XDR strain survived longer than those infected with MDR or sensitive strains. Lung pathology was reduced after XDR TB infection compared to sensitive or MDR TB infection. In summary, increasing degrees of drug resistance were associated with decreasing murine virulence in this collection of KZN strains as measured by all four virulence phenotypes. The predominance of HIV-infected patients in MDR and XDR TB outbreaks may be explained by decreased virulence of these strains in humans. |
| first_indexed | 2024-12-19T17:17:08Z |
| format | Article |
| id | doaj.art-f21c32cad75048df8fe5e5ff90955769 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T17:17:08Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f21c32cad75048df8fe5e5ff909557692022-12-21T20:12:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9495310.1371/journal.pone.0094953Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model.Kristen L Jurcic SmithDivey SainiSvetoslav BardarovMichelle LarsenRichard FrothinghamNeel R GandhiWilliam R JacobsA Willem SturmSunhee LeeBacterial drug resistance is often associated with a fitness cost. Large outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been described that predominately affect persons with HIV infection. We obtained four closely-related Mycobacterium tuberculosis strains (genotype F15/LAM4/KZN) from an outbreak in KwaZulu-Natal (KZN), South Africa, including drug-sensitive, MDR, and XDR clinical isolates. We compared the virulence of these strains in a murine model of aerosol M. tuberculosis infection for four phenotypes: (1) competitive in vivo growth in lung and spleen, (2) non-competitive in vivo growth in lung and spleen, (3) murine survival time, and (4) lung pathology. When mixtures of sensitive, MDR, and XDR KZN strains were aerosolized (competitive model), lung CFUs were similar at 60 days after infection, and spleen CFUs were ordered as follows: sensitive > MDR > XDR. When individual strains were aerosolized (non-competitive model), modest differences in lung and spleen CFUs were observed with the same ordering. C57BL/6, C3H/FeJ, and SCID mice all survived longer after infection with MDR as compared to sensitive strains. SCID mice infected with an XDR strain survived longer than those infected with MDR or sensitive strains. Lung pathology was reduced after XDR TB infection compared to sensitive or MDR TB infection. In summary, increasing degrees of drug resistance were associated with decreasing murine virulence in this collection of KZN strains as measured by all four virulence phenotypes. The predominance of HIV-infected patients in MDR and XDR TB outbreaks may be explained by decreased virulence of these strains in humans.http://europepmc.org/articles/PMC3986381?pdf=render |
| spellingShingle | Kristen L Jurcic Smith Divey Saini Svetoslav Bardarov Michelle Larsen Richard Frothingham Neel R Gandhi William R Jacobs A Willem Sturm Sunhee Lee Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. PLoS ONE |
| title | Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. |
| title_full | Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. |
| title_fullStr | Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. |
| title_full_unstemmed | Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. |
| title_short | Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model. |
| title_sort | reduced virulence of an extensively drug resistant outbreak strain of mycobacterium tuberculosis in a murine model |
| url | http://europepmc.org/articles/PMC3986381?pdf=render |
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